Dosing of drugs is carried out in a number of different ways in the medical service today. Within health care there is a growing interest in medical products based on administering drugs by inhalation of dry medicament powder directly to the airways and lungs of a patient. Interest focuses often on dry powder inhalers (DPI) because they offer effective, quick and user-friendly delivery of many substances formulated as dry powder doses for treatment of many different disorders. Because onset is faster and the efficacy of inhaled doses often are much higher than e.g. orally administered capsules or tablets, the inhalation doses need only be a fraction of the medicament powder mass in an oral capsule or tablet. Thus, there is an increasing demand for relatively low mass, inhalable, metered medicament doses, which require better filling methods and devices for making small and exact inhalation doses with low relative standard deviation (RSD).
Volumetric filling is by far the most common method of producing dry powder doses of medication drugs. Normally in a first step a quantity of powder is introduced into a receptacle of specified volume by gravitation, often aided by mechanical energy in the form of impaction or vibration, or the receptacle may be filled by suction force. Then in a second step, after stripping of possible surplus powder, the receptacle is moved to an emptying position, where the powder is unloaded from the receptacle by gravitation into a container such as a blister or capsule etc. A plurality of receptacles may be arranged in some kind of tool, which is adapted to a mechanism bringing a plurality of containers, e.g. blisters or capsules, in line with corresponding receptacles so that all doses of powder may be unloaded into the containers, one container per dose. The receptacle tool may be integrated into a filling machine such that the receptacles can be filled and emptied in a more or less continuous, cyclic fashion. Examples of prior art may be studied for instance in publications EP 0 319 131 B1, WO 95/21768, U.S. Pat. No. 5,826,633, U.S. Pat. No. 6,267,155 B1, U.S. Pat. No. 6,581,650 B2 and DE 202 09 156 U1.
Powders for inhalation need to be finely divided so that the majority by mass of particles in the powder is between 1 and 5 μm in aerodynamic particle size (AD). Powder particles larger than 5 μm tend not to deposit in the lung when inhaled, but to stick in the mouth and upper airways, where they are medicinally wasted and may even cause adverse side effects. However, finely divided powders are rarely free flowing, but are prone to adhere to all surfaces they come in contact with and the small particles tend to aggregate into lumps. This makes the metering of correct doses more difficult, since the bulk density of the powder may vary considerably from dose to dose even if the bulk density is constant when measured on powder quantities several magnitudes larger than the doses. Metering and filling correct quantities into a dose container is therefore more difficult with low dose masses. However, demand for doses from 5 mg down to 0.1 mg is increasing, putting pressure on the industry to improve methods and devices for metering and filling in the manufacturing stage as well as on dry powder inhalers to improve performance in terms of deaggregation and efficacy. Compacting the powder in the metering receptacle to reduce metering errors can be done, but care must be exercized so that agglomeration is not aggravated and to ensure that the agglomerates may still be de-aggregated by the inhaler.
Electrostatic forces, friction forces and van der Waal forces acting on particles become stronger than the gravitation force when particle size diminishes. Medication powders are very susceptible to electrostatic charging during transportation and handling of powders, especially in dry conditions. It is often necessary to remove as much as possible of electric charges of the particles by electric de-charging methods, particularly if the particles are small in size, in order to reduce the tendency of particles to stick to all surfaces of the handling equipment.
There is a need for improvements in methods and devices for precise metering of medicament doses of finely divided powders for inhalation and consistent, reliable filling of doses into suitable containers for use in inhaler devices.